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Computational KIR copy number discovery reveals interaction between inhibitory receptor burden and survival

Rachel M Pyke1, Raphael Genolet, Alexandre Harari

  • 1School of Medicine, University of California, San Diego, 9500 Gilman Dr., San Diego, CA 92093, USA, ramarty@ucsd.edu.

Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing
|March 14, 2019
PubMed

Insights

This study developed a new algorithm to determine killer immunoglobulin-like receptor (KIR) gene copy numbers from sequencing data. This approach reveals KIR gene variations are linked to survival in certain cancers, impacting immunotherapy.

Area of Science:

  • Immunology
  • Genetics
  • Bioinformatics

Background:

  • Natural killer (NK) cells and their killer immunoglobulin-like receptors (KIRs) are crucial for anti-tumor immunity.
  • High genetic polymorphism in KIR genes complicates genotype analysis and understanding their impact on cancer.
  • Current methods for determining KIR gene copy number are experimentally intensive.

Purpose of the Study:

  • To develop a computational algorithm for determining germline KIR gene copy number from whole exome sequencing (WES) data.
  • To apply this algorithm to a large cohort of cancer patients to investigate KIR gene variation.
  • To explore the association between KIR gene copy number variation and cancer patient survival.

Main Methods:

  • Developed a k-mer based computational algorithm to analyze WES data.
  • Quantified KIR gene sequences using k-mer distribution analysis.
  • Applied the algorithm to WES data from nearly 5000 cancer patients.

Main Results:

  • The algorithm accurately determined KIR gene copy numbers, showing high concordance with population expectations.
  • Analysis revealed an association between the burden of inhibitory KIR genes and patient survival in two cancer types.
  • This highlights the significance of KIR gene copy number variation in cancer phenotypes.

Conclusions:

  • The developed algorithm provides an efficient method for assessing KIR gene copy number from WES data.
  • KIR gene variation, specifically the burden of inhibitory KIR genes, is a significant factor in cancer survival.
  • Understanding KIR polymorphism is vital for advancing cancer immunotherapy and personalized medicine.

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